Improvement in the persistence of microbial asparaginase and glutaminase in the circulation of the rat by chemical modifications.
Three enzymes used in cancer chemotherapy (asparaginases from Escherichia coli and Erwinia carotovora and glutaminase from Achromobacter) were each reacted with four amino specific reagents (ethyl acetimidate, O-methylisourea, succinic anhydride, and formaldehyde/sodium borohydride). The half-lives of the modified enzymes measured in the blood of rats showed that guanidation, acetimidation and reductive alkylation were more likely to increase the persistence of the native enzymes than succinylation. However, the improvement in the persistence of any one enzyme after any one modification could not be predicted from the results with the others. It was concluded that changes in persistence caused by each modification were due to the different effects on the tertiary structure of each native enzyme. The advantages of chemical modification for increasing the persistence of enzymes over other methods such as encapsulation or aggregation are discussed.
D000421:Alcaligenes / Q000201:enzymology; D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood; D001215:Asparaginase / Q000097:blood*; D055598:Chemical Phenomena; D002621:Chemistry; D004885:Erwinia / Q000201:enzymology; D004926:Escherichia coli / Q000201:enzymology; D005972:Glutaminase / Q000097:blood*; D006207:Half-Life; D008239:Lysine; D051381:Rats
D000970:Antineoplastic Agents; D001215:Asparaginase; D005972:Glutaminase; D008239:Lysine